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PubMed1988

Effects of antimicrobial prophylaxis on colonization resistance.

The effect of antimicrobial agents on the intestinal microflora of patients undergoing colorectal surgery was examined. Two narrow spectrum agents, clindamycin and aztreonam, disturbed colonization resistance. This was preserved with the broad spectrum compound, imipenem. Ecological effects are difficult to predict and clinical studies of new antibiotics should include investigations of their impact on the normal human intestinal flora.

Adult↗
PubMed1995

Klebsiella pneumoniae infections in Greek hospitals. Dissemination of plasmids encoding an SHV-5 type beta-lactamase.

A total of 160 Klebsiella pneumoniae clinical strains consecutively isolated in 14 Greek hospitals in a three-month period was examined. Application of capsular typing using 72 monovalent antisera combined with phage-typing using a set of 15 Klebsiella-specific phages showed the absence of epidemic strains. However, 41% of the isolates examined displayed high level resistance to ceftazidime and aztreonam and, in most of the cases, to more than one aminoglycoside as well as to other antibacterial drugs. Nearly all of these multi-resistant strains were epidemiologically distinct on the basis of their capsular serotype and phage reactivity. After examination of 14 distinct strains, it was found that in nine cases, the resistance characters were readily transferred to Escherichia coli recipients through large self-transmissible plasmids (15-100 MDa). Six of the nine plasmids had equal molecular weight (60 MDa) and displayed similar fragment profiles upon digestion with restriction endonuclease EcoRI. Isoelectric focusing and hydrolytic studies showed that the prominent beta-lactamase produced by the transconjugants harbouring the 60 MDa plasmids and the respective K. pneumoniae parent strains, was an extended-spectrum beta-lactamase of the SHV-5 type. It appears that among K. pneumoniae strains isolated in Greek hospitals a significant resistance rate to both newer beta-lactams and amino-glycosides has been established through the acquisition of promiscuous multi-resistant plasmids which share a high degree of similarity.

Aztreonam↗
PubMed1990

Alteration of wound colonization by selective intestinal decontamination in thermally injured mice.

The effects of selective intestinal decontamination on the bacterial colonization of burn wounds were investigated in experimentally burned mice. Prior to scalding pathogen-free mice were pretreated with bacitracin to induce intestinal overgrowth of Enterobacteriaceae. Mice treated for 20 days postburn with oral aztreonam had significantly reduced enterobacterial wound colonization compared to untreated controls. This study indicates that burn wound colonization is altered by selective decontamination of the intestinal tract.

Animals↗
PubMed2006

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6: exploration of aromatic substituents.

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with aromatic substituents, were synthesized by the Suzuki cross-coupling method and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. By incorporating hydrophilic substituents onto the aryl nucleus, we found a morpholine analogue that possessed improved solubility, retained activity in vitro, and displayed potentiation activity in vivo in a rat model of P. aeruginosa pneumonia.

Animals↗
PubMed1998

A comparative investigation of the restorative effects of roxithromycin on neutrophil activities.

The effects of roxithromycin, a macrolide antibiotic, on neutrophil activities were investigated in six seriously handicapped patients with severe mental retardation. Neutrophil activities were evaluated by flow cytometry using a heparinized blood analysis method. All six patients showed decreased levels of neutrophil phagocytosis, intracellular killing, and CD11b expression. Treatment with roxithromycin in vitro selectively restored the decreased phagocytic and bactericidal activities of neutrophils in these patients. There was no significant restorative effect with cefaclor, ofloxacin, or aztreonam. These results suggest the need to consider therapeutic effects of antibiotics on neutrophil functions in patients at increased risk for bacterial infections due to decreased neutrophil activities.

Adolescent↗
PubMed2003

Antimicrobial spectrum of activity for meropenem and nine broad spectrum antimicrobials: report from the MYSTIC Program (2002) in North America.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides susceptibility data for participating medical centers where carbapenems are utilized. The activity of meropenem and nine broad-spectrum antimicrobial agents were assessed against 3,047 bacterial isolates collected during 2002 from 16 North American sites. The overall rank order of susceptibility of the 10 antimicrobial agents tested against Gram-negative isolates was: meropenem (98%) > imipenem (97%) > cefepime (95%) > tobramycin (93%) > piperacillin/tazobactam = gentamicin (92%) > ceftazidime (91%) > ciprofloxacin (87%) > aztreonam (86%) > ceftriaxone (74%). These results and those from previous years, demonstrate the continued excellent potency and spectrum of activity for meropenem. The utility of meropenem against Pseudomonas aeruginosa isolates has increased steadily with a rise in percent susceptibility each year from 78.2% in 1999 to a present rate of 93.1% susceptible. Conversely, we showed the susceptibility for ciprofloxacin against these same P. aeruginosa isolates has decreased from 82.9 to 72.3% susceptible over four years. Many medical centers have observed a decreased activity of some aminoglycosides, cephalosporins and fluoroquinolones due to increases in rates of extended-spectrum beta-lactamases, Amp C and other resistance mechanisms. Carbapenem resistance remains rarely documented and these beta-lactamase-stable agents appear to be an alternative treatment option for serious community-acquired or nosocomial infections in high risk patient populations.

Anti-Bacterial Agents↗
PubMed1996

Timed killing kinetic studies of the interaction between ciprofloxacin and beta-lactams against gram-negative bacilli.

Timed killing kinetic studies were performed with ciprofloxacin in combination with aztreonam, ceftazidime, piperacillin/tazobactam, and ticarcillin/clavulanic acid against three isolates each of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa. Each antimicrobial agent in the combination was tested at its MIC and at one-half and one-quarter of its MIC. Colony counts were determined at 0, 3, 5, and 7 hours. Synergy occurred most frequently at 7 hours and, when present, was most likely to occur when ciprofloxacin and the beta-lactam were tested at concentrations equal to their respective MICs. Synergy after 3 hours of incubation was not predictive of a synergestic interaction at 5 or 7 hours. Antagonism was noted in several instances, particularly when ciprofloxacin and the beta-lactam were combined at one-quarter of their respective MICs.

Anti-Bacterial Agents↗
PubMedDate not supplied

Validation of Etest for seven antimicrobial agents using regulatory criteria for the assessment of antimicrobial susceptibility devices.

Etest, a stable-gradient antimicrobial susceptibility test method (AB Biodisk, Solna, Sweden), was compared to the agar dilution method for tests with amikacin, tobramycin, aztreonam, cefdinir, cefprozil, ceftazidime and sparfloxacin. The study design followed recommended guidelines for 510(k) application by the U.S. Food and Drug Administration (FDA). Results demonstrated Etest accuracy (MIC +/- 1.0 log2 dilutions compared to agar dilution MIC) to be 90.4% with only one of 1150 comparisons showing a reproducible variation of 2 log2 dilutions. Categorical equivalency was > or = 92% for all drugs except ceftazidime (82 to 89%), but false-susceptible error was rare (< 0.1%). Etest was very reproducible (100% of results +/- 1.0 log2 dilution) and quality control results conformed to published MIC ranges. The Etest seems to render accurate results for these seven antimicrobial agents evaluated.

Amikacin↗
PubMed1998

Multicenter survey of the in vitro activity of four expanded-spectrum beta-lactams against consecutive contemporary clinical isolates.

A survey of the in vitro susceptibility of consecutive clinical bacterial isolates to cefotaxime, ceftazidime, cefpodoxime, and aztreonam was conducted at 10 North American medical centers during the first quarter of 1997. All four drugs had good activity against Enterobacteriaceae and fastidious Gram-negative bacteria and poor activity against enterococci and methicillin-resistant staphylococci. No significant trends in susceptibility to cefotaxime or ceftazidime were observed when compared with a previous similar survey. The use of cefpodoxime MIC > 2.0 micrograms/mL as a marker for extended-spectrum beta-lactamase production by Escherichia coli and Klebsiella spp. had good sensitivity, but the specificity was very poor for E. coli. Thus, at least for E. coli, this screening test seems to be of questionable value unless used to indicate the need for additional tests such as clavulanic acid inhibition. Disk diffusion zone diameters correlated well with the MICs for all four drugs and support the current interpretive criteria.

Anti-Bacterial Agents↗
PubMed2000

Surveillance of antimicrobial resistance in Escherichia coli strains isolated from pigs at Spanish slaughterhouses.

Antimicrobial resistance can make the efficient treatment of bacterial infections in humans and animals more difficult. Antimicrobial use in food animals may be one of the factors contributing to resistance. The Spanish surveillance network VAV has established a baseline of antimicrobial resistance in Escherichia coli strains from healthy pigs. Minimum inhibitory concentration and patterns of resistance to antimicrobials used in animals and humans were determined for 205 faecal strains isolated in a sampling frame of four slaughterhouses in Spain from 220 pigs in 1998. Higher levels of resistance were seen against antimicrobial agents authorised for use in food animals especially tetracycline, sulphonamides, trimethoprim and amoxycillin. All isolates were susceptible to antimicrobials employed mainly in humans such as ceftazidime, cefotaxime, imipenem, aztreonam and amikacin.

Abattoirs↗
PubMed2003

An approach for the evaluation of synergy between antimicrobials.

Synergy can be assessed by a variety of microbiological techniques. Mathematical modelling of synergy data can accomplish similar results and may provide more information than currently available techniques. In this study a combination of 1/4 MIC of aztreonam (AZTR) and 1 MIC of ciprofloxacin (CIPX) showed synergy against Pseudomonas aeruginosa in killing curve studies (based on the two log different criteria) at the end of 24 h. However, re-growth was always observed even when bactericidal concentrations of antibiotics were present. The surviving organisms showed a two-fold increase of MIC to CIPX after the studies and this resistance was not reversible. A mathematical model to quantitatively describe this observation is proposed.

Anti-Bacterial Agents↗
PubMed1994

The role of tyrosine 150 in catalysis of beta-lactam hydrolysis by AmpC beta-lactamase from Escherichia coli investigated by site-directed mutagenesis.

The kinetics of beta-lactam hydrolysis by wild-type AmpC beta-lactamase from Escherichia coli and three mutant proteins created by substitution of tyrosine 150 have been examined. The catalytic efficiency was decreased 10- to 1000-fold according to the substrate and mutant being studied. The effect of the mutation was much stronger with rapidly hydrolyzed substrates (e.g., cephalothin) than it was with slowly hydrolyzed substrates (e.g., ceftriaxone). With the latter substrates, the mutagenesis had a much stronger effect on apparent affinity than it did on rates of catalysis. Indeed, the enzyme appeared to be more reactive toward certain of the slowly hydrolyzed substances (e.g., methicillin, aztreonam, and ceftriaxone). These observations were not compatible with an obligatory role of tyrosine 150 in catalysis. The analysis of the effects of the mutation on activity was complicated by the observation of at least two, kinetically distinct, forms of the enzymes. It appeared that mutation of tyrosine 150 influenced the kinetic properties of one state and that this residue is involved in the partitioning of the enzyme between the different reactive states.

Acylation↗
PubMed2004

Using nanoparticle optics assay for direct observation of the function of antimicrobial agents in single live bacterial cells.

Multidrug resistance (MDR) has been reported in both prokaryotes and eukaryotes, underscoring the challenge of design and screening of more efficacious new drugs. For instance, the efflux pump of Pseudomonas aeruginosa (gram-negative bacteria) can extrude a variety of structurally and functionally diverse substrates, which leads to MDR. In this study, we present a new platform that studies modes of action of antibiotics in living bacterial cells (P. aeruginosa), in real-time, at nanometer scale and single-cell resolution using nanoparticle optics and single living cell imaging. The color index of silver (Ag) nanoparticles (violet, blue, green, and red) is used as the sized index (30 +/- 10, 50 +/- 10, 70 +/- 10, and 90 +/- 10 nm) for real-time measurement of sized transformation of the cell wall and membrane permeability at the nanometer scale. We have demonstrated that the number of Ag nanoparticles accumulated in cells increases as the aztreonam (AZT) concentration increases and as incubation time increases, showing that AZT induces the sized transformation of membrane permeability and the disruption of the cell wall. The results demonstrate that nanoparticle optics assay can be used as a new powerful tool for real-time characterization of modes of action of antimicrobial agents in living cells at the nanometer scale. Furthermore, studies of mutants of WT bacteria (nalB-1 and DeltaABM), suggest that an efflux pump (MexA-MexB-OprM) effectively extrudes substrates (nanoparticles) out of the cells, indicating that the MDR mechanism involves the induction of changes in membrane permeability and the intrinsic pump machinery.

Aztreonam↗
PubMed2003

Effect of basic amino acids on susceptibility to carbapenems in clinical Pseudomonas aeruginosa isolates.

We evaluated effects of medium composition, including basic amino acid content and pH, on susceptibility to carbapenems such as imipenem, panipenem and meropenem, in clinical isolates of Pseudomonas aeruginosa. Susceptibility to carbapenems was reduced by basic amino acids in the medium, while susceptibilities to ceftazidime and aztreonam were not. Among carbapenems, susceptibility to panipenem was most sharply reduced by addition of basic amino acids to 1:16 Mueller-Hinton agar (MHA). In 174 of 175 clinical isolates, MICs for carbapenems were affected to different degrees by medium composition. One isolate, in which MICs for carbapenems did not differ between MHA and 1:16 MHA, showed reduced production of porin (OprD). Our results suggest that susceptibility to individual carbapenems, especially panipenem, is difficult to evaluate based on MICs for other carbapenems determined on MHA. For a better prediction of antibiotic efficacy, it may be important to evaluate the susceptibility for each carbapenem individually.

Amino Acids, Basic↗
PubMed2002

Detection of extended spectrum beta-lactamases in the routine clinical microbiology laboratory.

AIMS: To compare three methods of confirming the presence of an extended spectrum beta-lactamase (ESBL) enzyme with the initial detection (i.e., screening) by the Vitek AMS. METHODS: Gram-negative bacteria which flagged as ESBL-positive in the Vitek GNS card, or were suspected of harbouring an enzyme, were further tested by each of the following methods: (a) combination disc test using cefpodoxime, ceftazidime and cefotaxime with and without clavulanate; (b) cefotaxime ESBL Etest; and (c) Jarlier keyhole method with cefpodoxime (10 microg), cefotaxime (5 microg) and aztreonam (30 microg) placed 15mm away from an augmentin (30 microg) disc. RESULTS: A total of 52 isolates were investigated, representing an 18-month time period. Fifty of these were positive by Vitek. Twenty-eight (56%) were confirmed by other methods (true positives). Of the 44% Vitek-positive/confirmatory test-negative (false positives), eight were Escherichia coli which was 53% of all E. coli tested. The majority of other false-positive isolates were Klebsiella oxytoca (24% overall) which were all Vitek- and Etest-positive but negative by the combination disc test. CONCLUSIONS: All ESBL-positive strains by Vitek should be confirmed by the combination disc test using all three antibiotics. This will enable differentiation of 'true' ESBLs from false-positive organisms, including K1 hyperbetalactamase-producing Klebsiella oxytoca and AmpC-producing organisms. The cefpodoxime combination discs gave the best differentiation in this study with only one ESBL organism being missed.

Adult↗
PubMed2000

Hospital-acquired brevundimonas vesicularis septicaemia following open-heart surgery: case report and literature review.

Brevundimonas vesicularis (B. vesicularis) is a pseudomonad rarely encountered in human infection. A case of nosocomial septicaemia with this organism following open-heart surgery is presented, with a review of the literature. The isolate demonstrated resistance to ciprofloxacin and aztreonam, which has not yet been reported. Treatment with piperacillin/tazobactam resulted in full recovery. A review of the literature reveals that B. vesicularis is a virulent organism involved in serious infections such as central nervous system infection or bacteraemia, some of which are nosocomial. Meanwhile, empiric therapy for B. vesicularis infection should include a broad-spectrum antimicrobial agent until susceptibility results are known.

Adult↗
PubMed1990

Acute prostatitis: which antibiotic to use first.

Six antimicrobial agents were administered to 48 patients (divided in 6 groups) who underwent prostatectomy. Half of the patients received the antibiotic in a single dose one hour before the operation and the rest in divided doses 24 hours before the operation. The concentration levels in serum and in prostatic tissue were measured for each of the antibiotics and for each mode of administration. The obtained ratios of prostatic tissue to serum concentrations and the relative antimicrobial activity to local pathogens of each agent indicate that the agent of choice for prostatic disease is netilmicin followed by aztreonam, cefuroxime and the ticarcillin-clavulanic acid combination.

Acute Disease↗
PubMedDate not supplied

Effect of highly potent antipseudomonal beta-lactam agents alone and in combination with aminoglycosides against Pseudomonas aeruginosa.

The activities of ticarcillin, cefsulodin, ceftazidime, aztreonam, and imipenem, formerly known as N-formimidoyl thienamycin, were evaluated alone and in combination with aminoglycosides against 56 clinical isolates of Pseudomonas aeruginosa, which were characterized by aminoglycoside susceptibility and content of aminoglycoside-modifying enzymatic activities. All beta-lactam agents were highly active against aminoglycoside-susceptible isolates, and with few exceptions the aminoglycoside-resistant isolates were susceptible to all of the beta-lactam agents except ticarcillin. Combinations of the beta-lactam agents with aminoglycosides frequently acted synergistically, but the effect of different beta-lactam agents in combination with an aminoglycoside against individual strains was unpredictable. The presence or absence of an aminoglycoside-modifying enzymatic activity had no observed effect on synergism with tobramycin. Killing-curve experiments with strains in the presence of concentrations of a beta-lactam and an aminoglycoside that were not bactericidal alone (one-fourth the minimal bactericidal concentration) showed synergistic bactericidal action against four strains that were tested. The results demonstrate the great activity of these newer antipseudomonal beta-lactam agents and their potential for synergism with aminoglycosides.

Aminoglycosides↗